I have previously characterized a growth factor specific for endothelial cells in culture. This growth factor is a high molecular weight moiety and is highly mitogenic for human umbilical vein endothelial cells in vitro. More recently, experiments from my laboratory have suggested that the high molecular weight form of endothelial cell growth factor (ECGF) may be composed of a complex of a low molecular weight ECGF peptide and a specific binding protein (ECGF-BP). In addition, experiments with bovine brain fibroblast growth factor (FGF) suggest that ECGF may be a precursor of FGF. The long range goals of this research are to establish by biochemical, immunological and biological criteria, the relationship between brain FGF and ECGF. Specifically, I will seek evidence to establish that brain FGF is a proteolytically modified form of ECGF as defined by the following expression: ECGF-BP--ECGF-BP + ECGF; ECGF or ECGF:ECGF-BP + Protease ----- FGF + ECGF (fragments). Initially, I plan to characterize the physical and chemical properties of ECGF. Using purified ECGF, I then plan to purify ECGF-BP and study the high molecular weight ECGF:ECGF-BP complex. The potential esterolytic and proteolytic activity of the binding protein will be studied and the role of the binding protein during post transcriptional modification of biosynthetic ECGF defined. The protease responsible for the conversion of ECGF to FGF will also be sought and characterized. These experiments will provide data to explain the relationship of ECGF to FGF and may affort new insights into the regulation of endothelial cell growth and the prevention of vascular thrombosis.